The present invention envisages wound dressing comprising of plant based cellulose nanocrystals matrix incorporated with nanosilver exhibiting excellent bactericidal and wound healing effects. The invention also relates to nanobiocomposite in the form of strip/film of virtually any shape or size as well as ointment and a production process thereof.
Wound healing is a complex event consisting of joint activities of many cell and tissue lineages proceeding through various biological pathways, depends upon numerous factors which are still under investigation. Wounds have been classified into various types: open and closed wound; acute and chronic wound; incision and excision wound. Initial phase of wound healing involves blood clot formation and inflammation. Inflammation is greatly enhanced if the wound of subject becomes a target of bacterial infection. Treatment of wounds such as, but not limited to, cuts, second and third degree burns, pressure ulcers, diabetic ulcers, surgical wounds, and various skin abrasions becomes difficult because of microbial infections. As inflammation subsides, the proliferation phase starts where the fibroblasts enter the wound site leading to formation of collagen fibrils responsible for wound closure and tissue regeneration. An impaired wound healing deals with prolonged inflammation, disjunction of wound tissue edges, and excessive formation of scar tissue without restoring normal structure and function of skin. A large number of efforts had already been put forward to overcome these problems related to impaired/delayed wound healing so as to inhibit the bacterial infection, promote the growth of fibroblasts and other specialized cells to enhance the rate of re-epithelization and eventually tissue regeneration. Some studies suggested that the capacity of moisture donation and absorption of wound exudates also play a role in optimal wound healing.
An ideal dressing material is not only meant to accelerate wound healing but also reduce loss of fluid from the wound, help to minimize pain and infection, provide protection to fragile skin, and should be non-adherent to wound. A variety of wound dressing materials are available in the global market to meet the needs and provide a better life to the patient. A wide variety of materials are available for the fabrication of wound dressings whose applicability depends upon the nature of wound to be treated. U.S. Pat. No. 6,140,257 describes the use of an absorbent, composite fiber as wound dressing comprising a matrix of 10% to less than 50% water insoluble alginate having dispersed therein at least 40% of another polysaccharide. A variety of other water absorbing active ingredients used in wound care products mentioned in prior art (U.S. 20130330417 A1) are chemically modified cellulose fibers, pectin fibers, alginate fibers, collagen fibers, chitosan fibers, hyaluronic acid fibers or other polysaccharide fibers.
Silver has been known as an antiseptic for ages. Silver, copper, zinc are used in the field from a long past. Even the nanocrystalline silver has been impregnated into gauze, alginate, hydrocolloids and foams for designing wound care products. These dressings are used for treatment of a particular type of wound depending upon their advantages. Gauzes used as dressing material adhere to the wound surface causing a pain and damage to neo-epithelium during removal of gauze. Some reports describe that alginate used in wound care products may cause long term foreign body type reaction. Hydrocolloids used in wound care have not been indicated for heavily exuding wounds and produce malodor. The foams may also produce excessive malodorous drainage which necessitates the frequent change of dressing. U.S. Patent No. 20120282348 A1 reports the use of silver hydrogels for the treatment of burn wounds by receiving or donating moisture. U.S. Pat. No. 5,514,657 A mentions about the topical antibacterial application of silver sulfadiazine and collagen for wound healing especially burn wounds. In-spite of their advantages, the products are generally expensive and exhibit less exudates absorption.
A large number of synthetic and natural polymers are present in market to be used in wound healing products. Synthetic polymers such as polyurethanes, polyvinylpyrolidone (PVP), polyethyleneoxide (PEO) and polyvinyl alcohol (PVA) can be used in combination with other synthetic or natural polymers to achieve great properties optimal for healing e.g. moisture retention, re-swelling capability, and absorption of wound exudates. Natural polymers like collagen and alginates have been exploited for wound dressing. Even though these possess good water absorption/donation capacity but biocompatibility and cost are the issues related to their use.
An alternate biopolymer, cellulose also possesses inherent characteristics responsible for accelerated wound healing. It is the most abundant, oldest, biocompatible, renewable bioresource present on the earth. Cellulose has high tensile strength because of its inherent hydrogen bonding structure. Cellulose nanocrystals (CNCs) or nanofibers are developed as a new class of nano-materials having wide range of utilities as a reinforcing agent in nanocomposites, and in biomedical field. The natural sources like plants, agricultural wastes, bacteria, tunicates have been considered as raw material for cellulose. The plant sources earlier used for isolation of CNCs include wheat straw, husk, soy hulls, banana, bamboo, agricultural wastes, wood or culm of some plants. EP 2513149 A1 describes the isolation of CNCs from vegetative biomass such as flex and hemp using ammonium persulphate. U.S. Patent No. 2008/0108772 describes a process for producing cellulose nano whiskers by treating microcrystalline cellulose with HCI, as well as a new extrusion method to produce a reinforced organic polymeric material. The production of cellulose nano whiskers using HCI hydrolysis required pure cellulosic materials (e.g. MCC) and the resulting cellulose nano whiskers had a large size distribution. A number of ways are known to isolate CNCs such as chemical, mechanical, enzymatic, and chemical combined with mechanical method. Still there is a need to optimize the process parameters using an appropriate methodology to produce CNCs, free from non-cellulosic impurities having narrow size distribution so as to make use of these isolated CNCs in biomedical areas especially wound care. Cellulose fiber and cotton fibers are most suitable for surgical operations and medical treatment in view of their excellent moisture absorbency, water absorbency, and flexibility. The bacteria Acetobacter xylinum has also been considered to isolate cellulose. Bacterial cellulose has been reported for wound healing application due to its high water uptake capacity and purity. U.S. Pat. No. 7,704,523 B2 describes the use of microbial derived cellulose for treatment of chronic wounds. U.S. Patent No. 20130211308 A1 describes the use of nanosilver coated bacterial cellulose for wound healing due to its water uptake potential. U.S. Pat. No. 7,390,499 B2 describes the use of a mixture of cellulose and microbiocide as a wound healing agent. The chemical composition of bacterial cellulose is almost similar to plant cellulose. The problem existing with the use of microbial cellulose is that it is difficult and expensive to manufacture. The bacterial strains lose their ability to synthesize cellulose during their growth in culture and they fail to maintain their integrity during application. Furthermore, manufacturing, processing and use of microbial cellulose fail to provide a continuous source of wound dressing used in different types of wounds. Bacterial cellulose having high water retaining capacity may also enhance the chances of bacterial infection due to excessive moisture around the wound site. There is a need to put efforts to isolate plant CNCs. Plant cellulose is easy to extract, environmentally benign, abundant in nature, renewable, biocompatible, cost effective, and have good water absorption capacity.
The prior art has failed to provide a wound dressing material which have the collective potential of optimum wound healing, ability of moisture management, antimicrobial activity, anti-inflammatory activity, and adequate biocompatibility. In the present invention, attempts have been made to isolate CNCs from Syzygium cumini plant leaves. To solve the aforementioned problems related to wound care products, designing of nanobiocomposite containing plant CNCs and nanocrystalline silver (AgNPs) is described to meet the criteria of ideal wound dressing as it has a synergistic role of water management and antimicrobial action suitable for promotion of wound healing. The biocompatible and cost effective wound dressing of present invention in the form of thin strip and ointment assist in wound healing by decreasing the rate of inflammation, promoting proliferation and granulation, decreasing scar formation, allowing epithelial migration, early collagen formation, increasing rate of wound closure and ultimately enhancing re-epithelization. Nanosilver particles incorporated in nanocellulose have anti-microbial, anti-inflammatory action and also help to minimize scarring. AgNPs help in conversion of fibroblasts into myofibroblasts which have an impact on wound closure. In addition to this, wound dressing of present invention neither degrade nor leave any residue at the wound site. The wound dressing does not adhere to the wounded skin while removal and does not cause any pain.